A2: Basolateral ciliogenesis, basal progenitor delamination, and the formation of the subventricular zone in developing neocortex

In the funding period 2009-2013, we showed that the release of midbodies, which may carry the somatic stem cell marker prominin-1 (CD133), occurs much more frequently after division of neural and other stem cells than cancer-derived cells. We also made the unexpected observation that in the developing neocortex, nascent basal progenitors (BPs) establish a basolateral rather than apical primary cilium, which precedes their delamination from the ventricle. In the 2013-2017 funding period, we propose to investigate basolateral ciliogenesis in greater detail, specifically: (i) to elucidate the underlying mechanism; (ii) to determine, by manipulating this mechanism, the biological significance of basolateral ciliogenesis for BP delamination and the formation of the subventricular zone (SVZ), a hallmark of neocortex evolution. First, we propose to determine the fate of the ciliary membrane during neural stem cell divisions. Second, we propose to investigate the differences between apical and basolateral ciliogenesis. Third, we propose to investigate whether differences in signaling via apical versus basolateral primary cilia contribute to the generation of nascent BPs and their delamination. Together, these three lines of investigations should provide insight into the role of basolateral cilia in BP generation and delamination, and thus the formation of the SVZ in the developing neocortex.